Genomes and Genes
Renal Medullary COX2 in Blood Pressure Regulation
Principal Investigator: Chuan Ming Hao
Abstract: As opposed to other tissues, the kidney exhibits abundant constitutive expression of inducible cyclooxygenase-2 (COX2) (18). Within the kidney, the vast majority of COX2 resides in the stromal/interstitial cells, with some COX2 expressed in the cortex in epithelial cells on macula densa and its adjacent fragment of cortical thick ascending limb. Studies indicate cyclooxygenase inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), including newly developed COX2 selective inhibitors (celecoxib, rofecoxib), cause sodium retention and hypertension in certain subsets of patients (21, 63, 64), pointing to an important role of renal COX2 mediated prostaglandins in regulating salt absorption and systemic blood pressure. Animal studies show renal medullary COX2 is markedly induced by high salt diet (69), consistent with the role of renal medullary COX2 in maintaining body sodium homeostasis. The present proposal will examine the hypothesis that high salt induced renal medullary interstitial (stromal) COX2 plays an important role in regulating renal medullary blood flow, salt excretion and maintaining systemic blood pressure. Defining the role of COX2 in renal interstitial cells should provide valuable information in identifying target molecule(s) or receptor(s) of renal COX2 mediated PGs. The proposed studies will have three specific aims: Specific Aim I: To examine the mechanism underlying high salt diet induced COX2 expression. Specific Aim II: To examine the role of renal medullary interstitial cell COX2 in modulating sodium excretion and maintaining blood pressure following high salt loading. Specific Aim III: To define the down-stream target of activated renal medullary COX2 expression.
Funding Period: 2005-07-15 - 2010-06-30
more information: NIH RePORT
- Sirt1 activation protects the mouse renal medulla from oxidative injuryWenjuan He
Nephrology Division, Vanderbilt University Medical Center School of Medicine, Nashville, Tennessee 37232, USA
J Clin Invest 120:1056-68. 2010..We therefore suggest that Sirt1 provides a potential therapeutic target to minimize renal medullary cell damage following oxidative stress...
- Renal function, bisphenol A, and alkylphenols: results from the National Health and Nutrition Examination Survey (NHANES 2003-2006)Li You
Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
Environ Health Perspect 119:527-33. 2011..Urinary excretion of bisphenol A (BPA) and alkylphenols (APs) was used as a biomarker in most previous studies, but no study has investigated whether urinary excretion of these environmental phenols differed by renal function...
- Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting ductMonica Carmosino
Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Am J Physiol Renal Physiol 292:F351-60. 2007..These findings further suggest distinct regulation of renal transport function by AVP through V1a and V2 receptors in the cortex vs. the medulla...
- Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J miceR Rao
Division of Nephrology, Medical Center North, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Diabetologia 50:452-60. 2007..In the current study, the effect of a highly specific peptide inhibitor of glycogen synthase kinase 3 (GSK3) (L803-mts) on glucose metabolism and BP was examined in a high-fat (HF) fed mouse model of diabetes...
- Expression of nestin in the podocytes of normal and diseased human kidneysWei Su
Division of Nephrology, Huashan Hospital, Institute of Nephrology, Fudan University, Shanghai, PR Chiina
Am J Physiol Regul Integr Comp Physiol 292:R1761-7. 2007..These studies suggest that nestin may play an important role in maintaining normal podocyte function in the human kidney...
- Physiological regulation of prostaglandins in the kidneyChuan Ming Hao
Division of Nephrology, Department of Medicine, Vanderbilt University, and Veterans Affair Medical Center, Nashville, TN 37232, USA
Annu Rev Physiol 70:357-77. 2008..COXs, prostanoid synthases, and prostanoid receptors should provide fruitful targets for intervention in the pharmacological treatment of renal disease...
- Increased dietary NaCl induces renal medullary PGE2 production and natriuresis via the EP2 receptorJian Chen
Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Am J Physiol Renal Physiol 295:F818-25. 2008..Renal medullary PGE(2) promotes renal sodium excretion via the EP2 receptor, thereby maintaining normotension in the setting of high salt intake...